In spite of their usefulness as analgesics, usage of opioids such as morphine and heroin are strictly limited. This is because these drugs induce side effects such as euphoria, respiratory depression or constipation. Further, multiple dosage of the drugs cause addiction. Thus, there has been a long-felt need to provide analgesics with reduced side effects.
From the above point of view, considerable pharmacological and biochemical studies have been carried out to identify opioid receptors and their endogenous ligands to prepare peptide and non-peptide opioid ligands for the receptors. In the recent past, amino acid sequences of mu- (.mu.-), delta (.delta.-) and kappa (.kappa.-) opioid receptor subtypes have been identified and reported. Subsequently, a novel receptor subtype was identified and termed ORL1-receptor, and Meunier, J.-C et al. reported the isolation and structure of the endogenous agonist of the receptor (Nature, Vol. 377, pp. 532-535, Oct. 12, 1995). It is suggested that the agonist compounds for ORL1-receptor be effective in neurogenic inflammation (Tips, Vol. 18, pp. 293-300, August 1997). It is also suggested that the agonist compounds be potent analgesics having less psychological side effects and addiction (D. Julius, Nature, Vol. 377, p. 476, Oct. 12, 1995).
WO 97/40035 discloses a 2-substituted 1-piperidyl benzimidazolyl compound substituted with a cycloalkyl group at the nitrogen atom of the piperidine group.